1) Field of the Invention
This invention relates to inhibitory agents against adsorption of herpesviruses to cells.
2) Description of the Related Art
It is well known that herpesviruses come to act as causative agents for various diseases. As an example of herpesviruses, there may be mentioned herpes simplex virus, which is one of the most typical represetantive of the family Herptoviridae consisting of varicella herpse zoster, cytomegalovirus, EB virus, etc. Herpes simplex virus contains double-stranded DNA with a molecular weight of 85 to 100.times.10.sup.6 daltons which is enclosed in a regular been known to have on its envelope six to eight species of glycoproteins with different antigenicities (Longnecker et al.; Proc. Natl. Acad. Sci. USA 84, 4302 (1987)).
This virus can be further classified into two subtypes, herpes simplex virus type 1 and type 2, which are considered to cause mainly stomatitis and genital herpes, respectively, but there is no strict distinction between these two subtypes. The typical diseases, for which this virus is regarded to be responsible, include not only the two diseases as described above but also a wide variety of diseases, such as keratitis, menigism, upper and lower respiratory tract infections and facial palsy. The virus, after initial infection, causes hosts to acquire inapparent infection, thereby making almost all human adults positive to its antibody. However, the antibody negativity ratio in adults has risen recently, and it is clarified that the initial infection of herpes simplex virus in expectant and nursing mothers causes extremely severe diseases in fetuses.
Development of various antiviral agents being directed toward this virus has heretofore been under progress, but a very few drug substances have been clinically confirmed so far for efficacy; only adenine arabinoside and aciclovir are clinically effective.
In recent years, anti-tumor factors contained in some components of Lentinus edodes have been in clinical use. Such anti-tumor factors, as exemplified by Krestin (Yanagawa et al.; "Gan to Kagakuryohou (Cancer and Chemotherapy), 11, 2155 (1985)) and Lentinan (Suga et al.; Cancer Research, 44, 5162 (1984)), are considered to owe their pharmacological activities to glycoproteins polysaccharide components contained therein. In addition, polysaccharides having sulfuric acid radicals such as dextran sulfate sodium were reported to exhibit activities against AIDS virus (Mitsuya et al., "Science", 248, 646 (1988)).
Furthermore, an aqueous extract of mycelial cultures of Lentinus edodes is called briefly "LEM", and a process for the production of the same is described in Japanese Patent Publication No. Sho 53-10117. LEM has been utilized as an agrochemical effective for the suppression of tobacco mosaic virus, and its therapeutic effect for hepatitis is also suggested (Harada et al.; "Kan-Tan-Sui, 14, No. 2, 327: Sugano et al.; "Cancer Letters", 17, 109 (1982); Suzuki et al.; Igaku no Ayumi (Progress on Medicine) 138 441 (1986)). LEM, when assayed with RNA of tobacco mosaic virus as a substrate, was confirmed to exhibit inhibition of the activity of reverse transcriptase derived from bird myeloma virus. This drug substance, when analyzed for its sugar compositon, was found to be specifically characterized by an extremely high content each of arabinose and xylose, indicating that the substance is clearly in contrast with Krestin and Lentinan which both have a sugar composition constituted almost exclusively of glucose.
Aciclovir as mentioned in the above, though it is considered to produce enhanced efficacy, shows a high degree of toxicity just as is the case with other nucleic acid antagonists. Under these circumstances, there is a strong demand for a safer and more effective medicine that can demonstrate therapeutic effect through different mechanism of action.
In addition, there has not yet been any satisfactory medicine available so far, that is capable of effectively inhibiting infection with the family Herpetoviridae inclusive of herpes simplex virus, without producing serious side effects to human body. This invention is intended to provide, from an entirely novel point of view, a medicine with a remarkably lowered degree of toxicity, which is quite different from nucleic acid analogs, in order to inhibit the adsorption of herpesviruses to cells and to block the proliferation of such viruses.